OBJECTIVE To explore the role of resistin in lung adenocarcinoma progression and its mechanism.METHODS The effect of resistin on A549 cells proliferation was detected by MTS assay.Wound-healing and transwell assays were used to evaluate the influence of resistin on A549 migration and invasion.Protein expression was detected by western blot.NF-k B translocation was evaluated by immunofluorescence.The expression of resistin in tumor tissue was assayed by immunohisto-chemical staining.RESULTS Compared with para-carcinoma tissues,resistin was overexpressed in tumor tissues.Resistin didn′t significantly affect A549 proliferation,but induced migration and invasion of A549.TLR4was the functional receptor of resistin in A549 cells,and resistin can bind to the second domain of TLR4.Resistin could increase p-EGFR by TLR4,induce PI3K/Akt phosphorylation and NF-k B translocation to nuclear.High resistin expression in lung adenocarcinoma tissues was correlated significantly with metastasis.Resistin was an independent predictor of overall survival.CONCLUSION Resistin promoted A549 migration and invasion by TLR4/EGFR/NF-k B pathway.Resistin was an independent prognosis predictor of lung adenocarcinoma.
GONG Wei-jingYIN Ji-yeLI Xiang-pingXIAO DiCUI Jia-jiaLI XiLIU Zhao-qian
Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods:A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial Registry
Chen-Yue QianYi ZhengYing WangJuan ChenJun-Yan LiuHong-Hao ZhouJi-Ye YinZhao-Qian Liu
